Enveloped viruses understood via multiscale simulation: computer-aided vaccine design

Shreif, Z.; Adhangale, Parag; Cheluvaraja, Srinath; Perera, Rushika; Kühn, Richard; Ortoleva, P.

doi:10.1007/978-1-4020-9741-6_19

Cited by 8 publications

(21 citation statements)

References 30 publications

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“…Density-like variable profiles: Release of drug molecules from a nanocapsule, the dynamics of enveloped viruses (Shreif et al, 2008; Shreif et al, 2009), and liquid crystal phase transitions (Lubensky, 1973; Nemtsov, 1977; Rothman et al, 1994; Shreif et al, 2009; Zwanzig, 2001). …”

Section: Methodsmentioning

confidence: 99%

Multiscale simulation of microbe structure and dynamics

Joshi¹,

Singharoy²,

Sereda³

et al. 2011

Progress in Biophysics and Molecular Biology

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A multiscale mathematical and computational approach is developed that captures the hierarchical organization of a microbe. It is found that a natural perspective for understanding a microbe is in terms of a hierarchy of variables at various levels of resolution. This hierarchy starts with the N -atom description and terminates with order parameters characterizing a whole microbe. This conceptual framework is used to guide the analysis of the Liouville equation for the probability density of the positions and momenta of the N atoms constituting the microbe and its environment. Using multiscale mathematical techniques, we derive equations for the co-evolution of the order parameters and the probability density of the N-atom state. This approach yields a rigorous way to transfer information between variables on different space-time scales. It elucidates the interplay between equilibrium and far-from-equilibrium processes underlying microbial behavior. It also provides framework for using coarse-grained nanocharacterization data to guide microbial simulation. It enables a methodical search for free-energy minimizing structures, many of which are typically supported by the set of macromolecules and membranes constituting a given microbe. This suite of capabilities provides a natural framework for arriving at a fundamental understanding of microbial behavior, the analysis of nanocharacterization data, and the computer-aided design of nanostructures for biotechnical and medical purposes. Selected features of the methodology are demonstrated using our multiscale bionanosystem simulator DeductiveMultiscaleSimulator. Systems used to demonstrate the approach are structural transitions in the cowpea chlorotic mosaic virus, RNA of satellite tobacco mosaic virus, virus-like particles related to human papillomavirus, and iron-binding protein lactoferrin.

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Section: Methodsmentioning

confidence: 99%

Multiscale simulation of microbe structure and dynamics

Joshi¹,

Singharoy²,

Sereda³

et al. 2011

Progress in Biophysics and Molecular Biology

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“…Because of the crucial role of carbohydrate–protein interactions in human biology, there is considerable interest in employing computational simulations to help characterize these systems and aid in the rational design of new therapeutics [10,39–41] and vaccines [42–44]. …”

Section: Protein–carbohydrate Interactionsmentioning

confidence: 99%

Molecular simulations of carbohydrates and protein–carbohydrate interactions: motivation, issues and prospects

Fadda

Woods

2010

Drug Discovery Today

172

122

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The characterization of the 3D structure of oligosaccharides, their conjugates and analogs is particularly challenging for traditional experimental methods. Molecular simulation methods provide a basis for interpreting sparse experimental data and for independently predicting conformational and dynamic properties of glycans. Here, we summarize and analyze the issues associated with modeling carbohydrates, with a detailed discussion of four of the most recently developed carbohydrate force fields, reviewed in terms of applicability to natural glycans, carbohydrate–protein complexes and the emerging area of glycomimetic drugs. In addition, we discuss prospectives and new applications of carbohydrate modeling in drug discovery.

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“…In the present implementation, it is optimized for non-enveloped viruses or the core of genomic complex of enveloped viruses, such dengue virus [43–44]. OPs constructed with orthogonal polynomials of atomic coordinates of a reference configuration or atomic displacements between two know configurations are introduced to capture the system slowly-varying nanoscale features.…”

Section: Introductionmentioning

confidence: 99%

All-Atom Multiscale Simulation of Cowpea Chlorotic Mottle Virus Capsid Swelling

2010

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An all-atom multiscale computational modeling approach, Molecular Dynamics/Order Parameter eXtrapolation (MD/OPX), has recently been developed for simulating large bionanosystems. It accelerates MD simulations and addresses rapid atomistic fluctuations and slowly-varying nanoscale dynamics of bionanosystems simultaneously. With modules added to account for water molecules and ions, MD/OPX is applied to simulate the swelling of cowpea chlorotic mottle virus (CCMV) capsid solvated in a host medium in this study. Simulation results show that the Nterminal arms of capsid proteins undergo large deviations from the initial configurations with their length extended quickly during the early stage of capsid swelling. The capsid swelling is a symmetry-breaking process involving local initiation and front propagation. The capsid swelling rate is ~0.25 nm/ns (npn) during early stage of the simulation and propagation of the structural transition across the capsid is roughly 0.6npn. The system conditions that affect swelling of the capsid are analyzed. Prospects for creating a phase diagram for CCMV capsid swelling and using predictions to guide experiments are discussed.

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Enveloped viruses understood via multiscale simulation: computer-aided vaccine design

Cited by 8 publications

References 30 publications

Multiscale simulation of microbe structure and dynamics

Multiscale simulation of microbe structure and dynamics

Molecular simulations of carbohydrates and protein–carbohydrate interactions: motivation, issues and prospects

All-Atom Multiscale Simulation of Cowpea Chlorotic Mottle Virus Capsid Swelling

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